Zinc ions play important roles in intracellular processes including enzyme catalysis, gene expression, apoptosis, neurotransmission and the like. Therefore, development of a zinc ion sensor is one of attractive fields for researchers of biological inorganic chemistry. Real time measurement of zinc ions and visualization of zinc ion distribution in living cells enable further elucidation of functions of zinc ions in bio-processes in vivo.
As compounds that specifically bind to zinc ions, N,N,N′,N′-tetrakis(2-pyridyl-methyl)ethylenediamine (TPEN) as a cell membrane-permeable zinc chelator is known (Helv. Chim. Acta, 50, 2330, 1967). Further, zinc ion sensors based on the photoinduced electron transfer (PET) mechanism have been extensively developed in recent years. In these sensors, a zinc ion binds to a heteroatom located near a fluorescent dye to inhibit PET, thereby a fluorescent property of the sensor molecule is switched on. As compounds wherein a zinc chelator moiety is introduced into a fluorescent fluorescein derivative, ZnAF-2 (J. Am. Chem. Soc., 122, 12399, 2000), Newport Green (the catalogue of Molecular Probes, Inc., “Handbook of Fluorescent Probes and Research Products” 8th edition, by Richard P. Haugland, pp. 805-817), Zinpyr-1 (J. Am. Chem. Soc., 122, 5644, 2000) and the like have been developed so far.

Furthermore, various zinc ion sensors based on quinoline chromophores have also been developed. These sensors utilize fluorescence induced by complexation (Chelation Enhanced Fluorescence, CHEF), and light emission mechanism thereof has been studied in detail by using 2,6-bis(quinolinecarboxy)methylpyridine (P2Q)/zinc complex (J. Comput. Chem. Jpn., 2, pp.57-62, 2003). As zinc ion sensors based on this quinoline chromophores, TSQ (J. Neurosci. Methods, 20, 91, 1987), Zinquin (Biochem. J., 296, 403, 1993) and the like have already been practically used. However, since these compounds form both fluorescent 1:1 complex and 1:2 complex with zinc ions, quantitative analysis may sometimes become difficult when they are used for the measurement of zinc ions. Further, these zinc ion sensors, except for a few of them such as ZnAF-2, suffer from problems in that they have a high level of background fluorescence, and they are readily affected by pH in the physiological pH range, i.e., pH from 6 to 8. Moreover, these zinc ion sensors also have a problem in that multiple steps are required for their synthesis, and therefore, they cannot be manufactured in a large scale at low cost.
